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Although displaying functional characteristics of both adaptive and innate immunity, \u03b3\u03b4 T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human \u03b3\u03b4 T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette\u2013Gu\u00e9rin vaccine. We investigated in vivo induction of innate memory in \u03b3\u03b4 T cells by Bacillus Calmette\u2013Gu\u00e9rin vaccination in healthy human volunteers by combining single-cell RNA sequencing technology with immune functional assays. The total number of \u03b3\u03b4 T cells and membrane markers of activation was not influenced by Bacillus Calmette\u2013Gu\u00e9rin vaccination. In contrast, Bacillus Calmette\u2013Gu\u00e9rin changed \u03b3\u03b4 T cells\u2019 transcriptional programs and increased their responsiveness to heterologous bacterial and fungal stimuli, including lipopolysaccharide and Candida albicans, as simultaneously characterized by higher tumor necrosis factor and interferon \u03b3 production, weeks after vaccination. Human \u03b3\u03b4 T cells in adults display the potential to develop a trained immunity phenotype after Bacillus Calmette\u2013Gu\u00e9rin vaccination.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad103","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T15:13:53Z","timestamp":1694013233000},"page":"149-163","source":"Crossref","is-referenced-by-count":40,"title":["BCG vaccination induces innate immune memory in \u03b3\u03b4 T cells in humans"],"prefix":"10.1093","volume":"115","author":[{"given":"Tsz K","family":"Suen","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn , Carl-Troll-Stra\u00dfe 31, 53115 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone J C F M","family":"Moorlag","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Computational Biology of Individualized Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Stra\u00dfe 7, 30625 Hannover , Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Str. 7, 30625 Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L Charlotte J","family":"de Bree","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-9013","authenticated-orcid":false,"given":"Valerie A C M","family":"Koeken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"},{"name":"Department of Computational Biology of Individualized Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Stra\u00dfe 7, 30625 Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera P","family":"Mourits","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Lemmers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-3125","authenticated-orcid":false,"given":"Jaydeep","family":"Bhat","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein , Campus Kiel, Arnold-Heller-Stra\u00dfe 3, 24105 Kiel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"},{"name":"Department of Computational Biology of Individualized Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Stra\u00dfe 7, 30625 Hannover , Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Str. 7, 30625 Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-9830","authenticated-orcid":false,"given":"Leo A B","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"},{"name":"Department of Medical Genetics, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy , Strada Victor Babe\u0219 8, Cluj-Napoca 400347 , Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim L","family":"Schultze","sequence":"additional","affiliation":[{"name":"Department of Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn , Carl-Troll-Stra\u00dfe 31, 53115 Bonn , Germany"},{"name":"Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases, University of Bonn , Venusberg-Campus 1\/9953127, Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8 , 6525 GA Nijmegen , Netherlands"},{"name":"Department of Computational Biology of Individualized Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Stra\u00dfe 7, 30625 Hannover , Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research , Feodor-Lynen-Str. 7, 30625 Hannover , 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